Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient.
Drosophila melanogaster
biophysics
developmental biology
quantitative biology
transcriptional dynamic
transcriptional modeling
transcriptional regulation
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
15 03 2023
15 03 2023
Historique:
received:
07
07
2021
revised:
03
09
2022
accepted:
21
12
2022
pmc-release:
15
03
2024
pubmed:
26
1
2023
medline:
21
3
2023
entrez:
25
1
2023
Statut:
ppublish
Résumé
How enhancers interpret morphogen gradients to generate gene expression patterns is a central question in developmental biology. Recent studies have proposed that enhancers can dictate whether, when, and at what rate promoters engage in transcription, but the complexity of endogenous enhancers calls for theoretical models with too many free parameters to quantitatively dissect these regulatory strategies. To overcome this limitation, we established a minimal promoter-proximal synthetic enhancer in embryos of Drosophila melanogaster. Here, a gradient of the Dorsal activator is read by a single Dorsal DNA binding site. Using live imaging to quantify transcriptional activity, we found that a single binding site can regulate whether promoters engage in transcription in a concentration-dependent manner. By modulating the binding-site affinity, we determined that a gene's decision to transcribe and its transcriptional onset time can be explained by a simple model where the promoter traverses multiple kinetic barriers before transcription can ensue.
Identifiants
pubmed: 36696901
pii: S2405-4712(22)00496-3
doi: 10.1016/j.cels.2022.12.008
pmc: PMC10125799
mid: NIHMS1868763
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
220-236.e3Subventions
Organisme : NICHD NIH HHS
ID : DP2 HD094655
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM139913
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008295
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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